Prevalence of the apolipoprotein E epsilon 4 allele in amyloid beta positive subjects across the spectrum of Alzheimer's disease

Niklas Mattsson*, Colin Groot, Willemijn J. Jansen, Susan M. Landau, Victor L. Villemagne, Sebastiaan Engelborghs, Mark M. Mintun, Alberto Lleo, Jose Luis Molinuevo, William J. Jagust, Giovanni B. Frisoni, Adrian Ivanoiu, Gael Chetelat, Catarina Resende Oliveira, Karen M. Rodrigue, Johannes Kornhuber, Anders Wallin, Aleksandra Klimkowicz-Mrowiec, Ramesh Kandimalla, Julius PoppPauline P. Aalten, Dag Aarsland, Daniel Alcolea, Ina S. Almdahl, Ines Baldeiras, Mark A. Buchem, Enrica Cavedo, Kewei Chen, Ann D. Cohen, Stefan Foerster, Juan Fortea, Kristian S. Frederiksen, Yvonne Freund-Levi, Kiran Dip Gill, Olymbia Gkatzima, Timo Grimmer, Harald Hampel, Sanna-Kaisa Herukka, Peter Johannsen, Koen Laere, Mony J. Leon, Wolfgang Maier, Jan Marcusson, Olga Meulenbroek, Hanne M. Mollergard, John C. Morris, Barbara Mroczko, Arto Nordlund, Sudesh Prabhakar, Oliver Peters, Lorena Rami, Eloy Rodriguez-Rodriguez, Catherine M. Roe, Eckart Ruther, Isabel Santana, Johannes Schroder, Sang W. Seo, Hilkka Soininen, Luiza Spiru, Erik Stomrud, Hanne Struyfs, Charlotte E. Teunissen, Frans R. J. Verhey, Stephanie J. B. Vos, Linda J. C. van Waalwijk Doorn, Gunhild Waldemar, Asa K. Wallin, Jens Wiltfang, Rik Vandenberghe, David J. Brooks, Tormod Fladby, Christopher C. Rowe, Alexander Drzezga, Marcel M. Verbeek, Marie Sarazin, David A. Wolk, Adam S. Fleisher, William E. Klunk, Duk L. Na, Pascual Sanchez-Juan, Dong Young Lee, Agneta Nordberg, Magda Tsolaki, Vincent Camus, Juha O. Rinne, Anne M. Fagan, Henrik Zetterberg, Kaj Blennow, Gil D. Rabinovici, Oskar Hansson, Bart N. M. Berckel, Wiesje M. Flier, Philip Scheltens, Pieter Jelle Visser, Rik Ossenkoppele*

*Corresponding author for this work

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Abstract

Introduction: Apolipoprotein E (APOE) epsilon 4 is the major genetic risk factor for Alzheimer's disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid beta(A beta) pathology. Methods: We included 3451 A beta+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE epsilon 4 prevalence in relation to age, sex, education, and geographical location. Results: The APOE epsilon 4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in A beta+ cognitively normal and A beta+ mild cognitive impairment (P <.05) but not in A beta+ AD dementia (P =.66). The prevalence was highest in Northern Europe but did not vary by sex or education. Discussion: The APOE E4 prevalence in AD was higher than that in previous studies, which did not require presence of A beta pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location. (C) 2018 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
Original languageEnglish
Pages (from-to)913-924
Number of pages12
JournalAlzheimer's & Dementia
Volume14
Issue number7
DOIs
Publication statusPublished - 1 Jul 2018

Keywords

  • APOE
  • Prevalence
  • Amyloid
  • PET
  • CSF
  • Alzheimer's disease
  • Mild cognitive impairment
  • Subjective cognitive decline
  • Age
  • Sex
  • Education
  • Geographical location
  • CEREBROSPINAL-FLUID BIOMARKERS
  • MILD COGNITIVE IMPAIRMENT
  • NATIONAL INSTITUTE
  • APOE GENOTYPE
  • ASSOCIATION WORKGROUPS
  • DIAGNOSTIC GUIDELINES
  • LONGITUDINAL COHORT
  • GLUCOSE-METABOLISM
  • CSF BIOMARKERS
  • OLDER-ADULTS

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